Nucleophiles reductive removal

The nucleophiles that are used for synthetic purposes include water, alcohols, carboxylate ions, hydroperoxides, amines, and nitriles. After the addition step is complete, the mercury is usually reductively removed by sodium borohydride, the net result being the addition of hydrogen and the nucleophile to the alkene. The regio-selectivity is excellent and is in the same sense as is observed for proton-initiated additions.17... 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

In brief, a wide range of 2-deoxyglycosides are available from glucals, either directly using proton or Lewis acids together with nucleophiles, or by haloalkoxyla-tion with subsequent reductive removal of the halide at C-2. 

Aryldiazonium salts, usually obtained from arylamines, undergo replacement of the diazonium group with a variety of nucleophiles to provide advantageous methods for producing aryl halides, cyanides, phenols and arenes by reductive removal of the diazo group. Coupling reaction of aryldiazonium salts with phenols or arylamines give rise to the formation of azo dyes. 

In the previous subsection, it was shown that the Ferrier reaction offers an opportunity to convert glycal derivatives into unsaturated sugar derivatives, which have an isolated double bond between C(2) and C(3). The Tipson-Cohcn reaction is another important reaction for the introduction of isolated double bonds.29 In this procedure, a cis or tram diols are converted into disulfonates (mesylates or tosylates) which are reductively eliminated with sodium iodide and zinc in refluxing DMF (Scheme 3.6a). In this reaction, the C(3) sulfonate is substituted by an iodide, which then is reductively removed by zinc with concomitant elimination of the second sulfonate moiety, introducing a double bond. Stereoelectronic effects make nucleophilic substitutions at C(3) more favourable than similar reactions at C(2) (see Section 3.2.3). Probably, the elimination proceeds through a boat conformation. In this case, the iodide and tosylate are in a syn relation. In most cases, E2 elimination proceeds via a transition state involving an anti orientation. Nevertheless, syn elimination becomes the dominant mode of reaction when structural features prohibit an anti orientation. 

The sulfur can be reductively removed by one of the many methods utilized for sulfur heterocycles. For the fused pyrimidine (703) zinc in acetic acid can be used (64JOC2135). In the 7-formylamino analogue (704), however, Raney nickel in aqueous ethanol was the best reagent for the reductive cyclization to form adenines (705) (78JOC960). It has been pointed out that nucleophilic substitution at C-7 in the [l,2,5]thiadiazolo[3,4-d]pyrimidine system easily takes place. This makes the compounds (704) readily available as key substances in this convenient approach to the synthesis of 9-substituted adenine derivatives. 

Tellurium species are also useful to remove several different types of substituents from organic compounds. In some cases, variation of the experimental conditions allows the reductive removal of a substituent to be performed selectively in the presence of other functional groups. Scheme 26109 113 shows the removal of different substituents mediated by nucleophilic tellurium species.6,11,12... 

The array of dienophiles amenable to these hetero Diels-Alder reactions is not limited to enol ethers and enamines since allylsilanes and simple alkenes have also been successfully employed [370, 371]. More recently, it has been shown that methoxy allenes such as 4-41 undergo formation of 6H-l,2-oxazines 4-43 upon cycloaddition to nitrosoalkenes such as 4-34 and subsequent tauto-merisation of the intermediate exo-methylene compound 4-42 (Fig. 4-9) [372, 373]. In these studies, 4-43 proved to be a versatile synthetical intermediate allowing oxidative demethylation or reductive removal of the methoxy group as well as nucleophilic substitutions after the generation of an azapyrylium ion [372 - 374]. Furthermore, ring contraction reactions of these oxazines leading to pyrroles [373] and y-lactames [375] are known. 

Most methods in the literature for reductive removal of a-substituents involve either electron transfer or nucleophilic cleavage, but other mechanistic pathways have been encountered with certain reagents or... 

An alternative route to chiral p-lactams was provided by reactions of electron-deficient isocyanates with chiral nucleophilic alkenes such as vinyl ethers or vinyl acetates. Chlorosulfonyl isocyanate (CSI), a commonly used reactive isocyanate [34], undergoes stereospecific 5-yn-addition to alkenes. The chlorosulfonyl group can subsequently be reductively removed from the nitrogen atom. It has been shown that reactions between CSI and (Z)- and ( )-alkenyl ethers stereoselectively give cA-3,4-disubstituted azetidinones from (Z)-olefins and tmns-3,4-... 

Another type of mechanism operates in the synthesis of amino acids by electrore-ductive coupling of alkyl halides with Schiff bases in DMF in these reactions the alkyl halide chosen is reduced at less negative potentials than the azomethine derivative of an a-ketoester, and the coupling is proposed to be a nucleophilic addition of an alkyl anion [Eq. (7)] to the azomethine compound, [Eq. (8)] the benzyl group is afterward reductively removed [32,33] ... 

The first step when using sulfones in the synthesis of natural products consists of the formation of the new C-C bond. This process is normally performed using the sulfone as a nucleophile via the corresponding a-sulfonyl carbanion. Three different strategies are normally employed alkylation of a-sulfonyl carban-ions followed by reductive removal of the sulfonyl group, acylation of a-sulfonyl carbanions followed by reductive removal of the sulfonyl group, and finally, reaction of a-sulfonyl carbanions with activated multiple bonds followed by reductive desulfonylation. 

ABSTRACT. Toluene radical anion, generated by dissolving potasssium metal in toluene by the assistance of dicyclohexano-18-crown-6, has been proved to be especially effective for reductive removal of fluorine atom from unactivated alkyl fluorides that resist common reduction conditions. Stereochemical and mechanistic aspects of the present method is discussed. In connection with the preparation of substrates the effect of dipolar aprotic solvents on the nucleophilic fluorination with potassium fluoride/dicyclohexano-18-crown-6 system was also examined, and sulfolane or N,N-dimethylformamide was shown to be a solvent of choice. 

Numerous examples of the removal of halogen substituents during the saturation of the pyridine nucleus (p. 264) and the reduction of substituents attached to it (pp. 267, 284) have been recorded. In nucleophilic halogen exchange, reductive removal of a halogen substituent is sometimes caused by the use of hydriodic acid (p. 230). Hydriodic acid and phosphorus replace 2- and 4-halogen substituents selectively, Hydriodic acid and zinc with acid give similar results . 

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